Estrogen/Androgen Meds

• Estrogen

  • Bind to nuclear receptors and increase the rate of synthesis of DNA, RNA, and some proteins, diffuse across the cell membrane and bind w/ receptor proteins to form an activated steroid-receptor complex that interacts w/ nuclear chromatin to initiate hormone specific synthesis of RNA, DNA and specific proteins
  • Nausea, breast tenderness, edema
  • Increased risk of endometrial and breast cancer, MI, stroke, PE, DVT
  • Available as emulsions, gel, spray, creams, tablets vaginal rings, injections; use lowest effective dose for shortest time possible
• Estrogen clinical use

  Contraception, postmenopausal HRT, HRT in premenopausal pt w/ estrogen deficiency, prevention of osteoporosis (not 1st line option, reduces resorption and increases BMD), relief of vasomotor sx and vulvovaginal atrophy, w/o hysterectomy → combo of estrogen/progestin but w/ hysterectomy → estrogen alone
• Selective Estrogen Receptor Modulators

  • Results in activations of estrogenic pathways in some tissues and blockade of pathways in others
  • Hot flashes, sweating, nausea, peripheral edema, leg cramps (raloxifene)
  • Contraindicated in pregnancy, hx of DVT or PE
  • BBW:
  • Tamoxifen: endometrial hyperplasia and malignancies, increased risk of stroke and PE
  • Raloxifene: increased risk of PE, DVT, death d/t stroke in postmenopausal women w/ CHD or risk for major coronary events
• SERM clinical use

  Breast cancer and prevention (tamoxifen), osteoporosis and breast  ca prophylaxis(raloxifene), off label → prostate ca prophylaxis, malignant melanoma, atrophic vaginitis
• Progestins

  • Promotes development of secretory endometrium to accommodate embryo, in second half of cycle → inhibit production of gonadotropin to prevent further ovulation, if conception → maintains endometrium and reduces contractions, if conception does NOT occur → rapid decline of progesterone stimulates menstruation
  • Headache, depression, weight gain, changes in libido, acne and hirsutism, increase potassium (drospirenone)
  • Half life 1-2 days except medroxy which is 40-50 days and gives 3 months of contraception, etonogestrel available as subdermal implantation for up to 3 years
• Progestin clinical use

  Contraception (often combo w/ estrogen), tx hormone deficiency, control dysfunctional uterine bleeding, dysmenorrhea, endometriosis, infertility
• Androgens

  • Bind to specific nuclear receptor in a target cell, testosterone first converted by 5-alpha reductase to DHT which then binds to the receptor
  • Weight gain, acne, decreased breast size, deepening voice, increased libido, increased hair growth, increase LDL:HDL ratio, edema, male pattern baldness, menstrual irregularities, priapism, impotence, decreased spermatogenesis, gynecomastia, virilization in children
  • Contraindicated in prostate/breast cancer, increased PSA, sleep apnea, polycythemia, hepatic disease, pregnancy
  • BBW = Virilization in children secondarily exposed
• Androgens

  • Available IM (least expensive and need frequent), transdermal patch (site rxn common), topical gel (best tolerated, do not wash or touch another person's skin for 4-6 hours), subcutaneous implant (3-6 months, not routine), buccal (rare), oral no longer preferred d/t hepatotoxicity
  • Testosterone levels, liver function, fasting lipid panel, PSA, hgb/hct
  • Used for primary or secondary hypogonadism in males, anabolic steroids, danazol → endometriosis, fibrocystic breast, unapproved uses → increase lean body mass, muscle strength and endurance in athletes
• Contraceptives

  • Increased risk of cervical cancer d/t decreased barrier protection
  • Contraindicated in cerebrovascular disease, pregnancy, should not be used in women smokers > 35
  • Interactions: some antibiotics and CYP3A4 inducers may decrease efficacy